Further evidence supporting the hypothesis that mutant ATXN3 promotes an accumulation of soluble K63-Ub proteins comes from our observation of increased levels of K63-Ub in SCA3 NPCs, but not CTRL NPCs, upon autophagy inhibition (Figure 6C), and from an earlier report demonstrating impaired autophagy and the accumulation of large autophagosome-like vesicles in SCA3 disease brain (Sittler et al., 2017). Here, ATXN3 is linked to Spinocerebellar ataxia type 3.